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Background Negative-pressure wound therapy (NPWT) promotes angiogenesis and granulation, in part by strain-induced production of growth factors and cytokines. As their expression profiles are being unravelled, it is pertinent to consider the mode of action of NPWT at the molecular level. Methods MEDLINE (January 1997 to present), Embase (January 1997 to present), PubMed (no time limit), the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles that evaluated the influence of NPWT on growth factor expression quantitatively. Results Sixteen studies met the inclusion criteria. Tumour necrosis factor expression was reduced in acute and chronic wounds, whereas expression of interleukin (IL) 1β was reduced in acute wounds only. Systemic IL-10 and local IL-8 expression were increased by NPWT. Expression of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor β and platelet-derived growth factor was increased, consistent with mechanoreceptor and chemoreceptor transduction in response to stress and hypoxia. Matrix metalloproteinase-1, -2, -9 and -13 expression was reduced but there was no effect on their enzymatic inhibitor, tissue inhibitor of metalloproteinase 1. Conclusion Cytokine and growth factor expression profiles under NPWT suggest that promotion of wound healing occurs by modulation of cytokines to an anti-inflammatory profile, and mechanoreceptor and chemoreceptor-mediated cell signalling, culminating in angiogenesis, extracellular matrix remodelling and deposition of granulation tissue. This provides a molecular basis for understanding NPWT.

In the Caledonides of northwest Scotland, two independent geothermometers (Fe-Mg exchange and quartz c-axis fabric opening angle) are used to characterize the thermal structure of the lower part of the Scandian (435–420 Ma) orogenic wedge within the Moine, Ben Hope and Naver-Sgurr Beag thrust sheets. Traced from west (foreland) to east (hinterland), Fe-Mg exchange thermometry yields peak or near-peak temperatures ranging from 484 ± 50 °C to 524 ± 50 °C in the immediate hangingwall of the Moine thrust to 601 ± 50 °C in the immediate hangingwall of the Ben Hope thrust, to 630 ± 50 °C in the Naver thrust sheet. Preserved metamorphic facies and textural relationships are consistent with thermometric estimates. Deformation temperatures calculated from quartz c-axis fabric opening angles across two similar orogen-perpendicular transects also yield systematic increases (Glen Golly – Ben Klibreck, 520–630 °C; Ullapool-Contin, 465–632 °C) traced towards the Naver and Sgurr Beag thrusts. In addition, deformation temperatures show a pronounced increase along the leading edge of the Moine thrust sheet moving south towards the Assynt window, which is interpreted to reflect deeper exhumation of the thrust plane above the Assynt footwall imbricate stack. Because temperatures calculated from metamorphic assemblages are within error of the quartz fabric-derived deformation temperatures that are of demonstrably Scandian age, the metamorphic sequence between the Moine and Naver-Sgurr Beag thrusts is interpreted to have developed during the Scandian orogeny. Integration of our results with previous 2D thermal-mechanical studies allows development of new conceptual thermal-kinematic models of Scandian orogenesis that may be broadly applicable to other collisional systems. Furthermore, it highlights the critical nature of coupling between orogen kinematic and thermal evolution.

Tujuan yang ingin dicapai dalam penelitian ini adalah untuk memperoleh informasi adat Nias yang mempengaruhi pola tindakan dan pola budaya Nias terhadap perempuan serta Menganalisa kedudukan perempuan dalam keluarga di Nias serta hal-hal yang mempengaruhinya. Untuk mencapai tujuan tersebut maka penulis menggunakan metode kualitatif untuk mengekploitasi, mengkaji nuansa sikap yang samar-samar, dan memahami makna lebih mendalam tentang perilaku Masyarakat Nias terhadap perempuan. Untuk itu, teori yang digunakan adalah teori feminis. Nias menganut budaya patriakha yang di dalamnya terjadi bias, namun budaya patriaakha dan bias gender yang terjadi sangat berbeda dengan budaya patriakha dan bias gender di tempat-tempat yang lain. Di satu sisi perempuan ditempatkan pada posisi yang paling tinggi yakni sebagai manifestasi dewi (Inada Silewe Hai Nazarata) yang dinyatakan dalam perilaku setiap hari terhadap perempuan; perempuan selalu diagungkan, dihormati, di dengar dan dicintai. Perempuan sebagai ibu dipercaya menentukan hari pernikahan putrinya, dipercaya sebagai pengelola rumah tangga, sebagai juru damai baik di keluarga batih maupun keluarga besar. Di sisi lain perempuan ditempatkan pada kedudukan yang paling rendah sebagai manusia; sebagai anak perempuan hanya sebagai pribadi titipan di rumah orang tuanya, sebagai istri perempuan mengalami diskriminasi, kekerasan dalam rumah tangga, beban ganda, ditempatkan sebagai kelas subordinat. Penindasan terhadap perempuan tidak hanya dilakukan oleh laki-laki, tetapi juga oleh perempuan di mana hal ini dilakukan atas legitimasi budaya dan agama Kristen. Melalui penelitian ini, peneliti ingin mengangakat filosophi yang mengalami pergeseran magna dan memberi sumbangan pemikiran bagi masyarakat akan harkat dan martabat perempuan sebagai pribadi yang harus diperlakukan adil dan sama seperti lai-laki.

Although host genetics influences susceptibility to Mycobacterium tuberculosis, the human genes regulating pathogenesis remain largely unknown. We used M. tuberculosis-stimulated macrophage gene expression profiling in conjunction with a case-control genetic association study to discover epiregulin (EREG), as a novel candidate tuberculosis (TB) susceptibility gene. Using a genome-wide association study dataset, we found that among the 21 genes with greater than 50-fold induction, EREG had the most polymorphisms associated with TB. We genotyped haplotype-tagging polymorphisms in discovery (N=337 cases, N=380 controls) and validation (N=332 cases) datasets and an EREG polymorphism (rs7675690) was associated with susceptibility to TB (genotypic comparison; corrected P=0.00007). rs7675690 was also associated more strongly with infections caused by the Beijing lineage of M. tuberculosis when compared with non-Beijing strains (controls vs Beijing, OR 7.81, P=8.7 × 10 -5; non-Beijing, OR 3.13, P=0.074). Furthermore, EREG expression was induced in monocytes and peripheral blood mononuclear cells stimulated with M. tuberculosis as well as TLR4 and TLR2/1/6 ligands. In murine macrophages, EREG expression induced by M. tuberculosis was MYD88- and TLR2-dependent. Together, these data provide the first evidence for an important role for EREG as a susceptibility gene for human TB. © 2012 Macmillan Publishers Limited All rights reserved.

Nesquehonite, Mg(HCO3)(OH).2H2O or MgCO3.3H2O, was named after its type locality in Nesquehoning, Pennsylvania, USA. The structure of nesquehonite can be envisaged as infinite chains of corner sharing MgO6 octahedra along the b-axis. Within these chains CO32- groups link 3 MgO6 octahedra by two common corners and one edge. This structural arrangement causes strong distortion of the octahedra. Chains are interconnected by hydrogen bonds only, whereby each Mg atom is coordinated to two water ligands and one free water molecule is located in between the chains [1, 2]. Under natural conditions nesquehonite can form in evaporites depending on the availability of Mg2+ ions in solution relative to other cations, such as Ca2+ [3-5]. Additionally, nesquehonite occurs as an alteration product in the form of scales or efflorescences on existing carbonate rocks, serpentine, or volcanic breccias [6-11]. Interestingly it has also been observed on the surface of a limited number of meteorites found in Antarctic regions, where it has formed by reactions of the meteorite minerals with terrestrial water and CO2 at near freezing temperatures [12-16]. Nesquehonite has also been identified on the surfaces of manmade materials, such as bricks and mortar [17, 18]. The synthesis of nesquehonite forms a continuation of our work on the synthesis and study of the vibrational spectroscopy of natural and synthetic minerals in the hydroxide (brucite, gibbsite, boehmite, etc.)[19-23], carbonate (cerussite, azurite, malachite, etc.)[24-26] and hydroxycarbonate (hydrotalcite)[21, 27-32] groups. This work aims at describing a simple method for the synthesis of nesquehonite and the detailed characterization of the structure and morphology by X-ray diffraction (XRD), vibrational spectroscopy and scanning electron microscopy (SEM).

Cystic fibrosis is a serious disorder. Research into the treatment of affected individuals is in progress, but a cure is not expected in the near future. In this review, we demonstrate that prenatal screening for cystic fibrosis meets the requirements for a worthwhile screening programme. We explain the reasons that have led us to conclude that one approach ('couple screening') is the method of choice. The couple-based approach calls for reporting results to the couple as a unit. Only if both parents are found to be carriers is the result designated screen-positive and an amniocentesis or chorionic villus sampling offered. This offers a substantial reduction in the proportion of women with unaffected pregnancies with positive results (the false-positive rate) compared with other methods without reducing the detection of affected pregnancies. It also avoids creating a screen-positive group for which no definitive diagnosis is available. This is a problem with other screening methods. The couple method can achieve a 72% detection rate for a 0.1% false-positive rate. The screening method is simple, non-invasive, reliable, safe and reasonably cost effective. Existing programmes have shown that screening using this method is acceptable to health care professionals and patients. Setting up a national prenatal screening programme for cystic fibrosis is timely and should be implemented using the couple screening method.

To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD.An unselected series of 67 individuals participating in the Mayo Alzheimer's Disease Research Center/Alzheimer's Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak.Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle--only degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all p0.001) were observed between hippocampal volume and Braak and Braak stage (r = -0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score (r = 0.60), and between MMSE score and Braak and Braak stage (r = -0.41).Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = -0.63, p = 0.001]) and consequent cognitive status.

Background: Not all breast cancer patients benefit from neoadjuvant or adjuvant therapy, resulting in considerable undertreatment or overtreatment. New insights into the role of tumor-infiltrating immune cells suggest that their composition, as well as their functionality, might serve as a biomarker to enable optimal patient selection for current systemic therapies and upcoming treatment options such as immunotherapy. Methods: We performed several complementary unbiased in silico analyses on gene expression profiles of 7270 unrelated tumor samples of nonmetastatic breast cancer patients with known clinical follow-up. CIBERSORT was used to estimate the fraction of 22 immune cell types to study their relations with pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). In addition, we used four previously reported immune gene signatures and a CD8+ T-cell exhaustion signature to assess their relationships with breast cancer outcome. Multivariable binary logistic regression and multivariable Cox regression were used to assess the association of immune cell-type fractions and immune signatures with pCR and DFS/OS, respectively. Results: Increased fraction of regulatory T-cells in human epidermal growth factor receptor 2 (HER2)-positive tumors was associated with a lower pCR rate (odds ratio [OR] = 0.15, 95% confidence interval [CI] = 0.03 to 0.69), as well as shorter DFS (hazard ratio [HR] = 3.13, 95% CI = 1.23 to 7.98) and OS (HR = 7.69, 95% CI = 3.43 to 17.23). A higher fraction of M0 macrophages in estrogen receptor (ER)-positive tumors was associated with worse DFS (HR = 1.66, 95% CI = 1.18 to 2.33) and, in ER-positive/HER2-negative tumors, with worse OS (HR = 1.71, 95% CI = 1.12 to 2.61). Increased fractions of gamma delta T-cells in all breast cancer patients related to a higher pCR rate (OR = 1.55, 95% CI = 1.01 to 2.38), prolonged DFS (HR = 0.68, 95% CI = 0.48 to 0.98), and, in HER2-positive tumors, with prolonged OS (HR = 0.27, 95% CI = 0.10 to 0.73). A higher fraction of activated mast cells was associated with worse DFS (HR = 5.85, 95% CI = 2.20 to 15.54) and OS (HR = 5.33, 95% CI = 2.04 to 13.91) in HER2-positive tumors. The composition of relevant immune cell types frequently differed per breast cancer subtype. Furthermore, a high CD8+ T-cell exhaustion signature score was associated with shortened DFS in patients with ER-positive tumors regardless of HER2 status (HR = 1.80, 95% CI = 1.07 to 3.04). Conclusions: The main hypothesis generated in our unbiased in silico approach is that a multitude of immune cells are related to treatment response and outcome in breast cancer.

Sewage contamination in shallow lake sediments is of concern because the pathogens, organic matter and nutrients contribute to the deterioration of the water-bodies' health and ecology. Sediment cores from three shallow lakes (Coneries, Church and Clifton Ponds) within Attenborough nature reserve located downstream of sewage treatment works were analysed for TOC, C/N, δ(13)C, δ(15)N, bacterial coliforms and faecal sterols. (210)Pb and (137)Cs activities were used to date the sediments. Elemental analysis suggests that the source of organic matter was algal and down profile changes in δ(13)C indicate a possible decrease in productivity with time which could be due to improvements in sewage treatment. δ(15)N for Coneries Pond are slightly higher than those observed in Church or Clifton and are consistent with a sewage-derived nitrate source which has been diluted by non-sewage sources of N. The similarity in δ(15)N values (+12 ‰ to +10 ‰) indicates that the three ponds were not entirely hydrologically isolated. Analysis by gas chromatography/mass spectrometry (GC/MS) reveals that Coneries Pond had sterol concentrations in the range 20 to 30 μg/g (dry wt.), whereas, those from Clifton and Church Ponds were lower. The highest concentrations of the human-sourced sewage marker 5β-coprostanol were observed in the top 40 cm of Coneries Pond with values up to 2.2 μg/g. In contrast, Church and Clifton Pond sediments contain only trace amounts throughout. Down-profile comparison of 5β-coprostanol/cholesterol, 5β-coprostanol/(5β-coprostanol+5α-cholestanol) and 5β-epicoprostanol/coprostanol as well as 5α-cholestanol/cholesterol suggests that Coneries Pond has received appreciable amounts of faecal contamination. Examination of 5β-stigmastanol (marker for herbivorous/ruminant animals) down core concentrations suggests a recent decrease in manure slurry input to Coneries Pond. The greater concentration of β-sitosterol in sediments from Church and Clifton Ponds as compared to Coneries is attributed in part to their greater diversity and extent of aquatic plants and avian faeces.

Background With the high prevalence rate of HIV and Hepatitis B virus infections in sub-Saharan Africa, infected surgical patients, especially those with fresh open wounds, pose significant danger of occupationally-acquired infections to health workers. Method A two-year double blind study aimed at determining the seroprevalence rates of HIV and Hepatitis B virus infections among trauma patients with fresh open wounds in North Central Nigeria. Results There were 134 patients with fresh open wounds in this study; their ages ranged between 17-80 years with a mean of 30.9 +/-9.6 years and the male:female ratio was 5:1. All the patients were tested for both HIV and Hepatitis B virus infections. Six(4.5%) patients were positive for HIV-1 while 95(70.9%) patients were positive for Hepatitis B. In all, 3(2.2%) male and 3(2.2%) female patients tested positive for HIV-1 while 77(57.4%) males and 18(13.4%) females tested positive for Hepatitis B; 5(3.7%) patients tested positive for both HIV and Hepatitis B. Though every social class was represented, HIV infection rate was higher in Social Class V than in Social Class 1 but the class incidence rate for Hepatitis B was about the same ranging between 1.2 and 1.6 for both the upper and lower classes. The significance of this study was that the incidence of Hepatitis B virus infection in trauma patients was remarkably higher than the incidence of HIV infection. The implication is that emphasis on control of exposure of health care workers to blood borne infections in the workplace should be as strong for Hepatitis B virus infection as it is for HIV. Conclusion The main finding of this study was the determination of the seroprevalence of HIV and Hepatitis B virus infections in trauma patients with open wounds which underpinned the dangers they pose to health care workers.

Various molecules expressed on the surface of platelets have been shown to mediate the protective or deleterious role of these cells in immuno-inflammatory mechanisms. Increasing evidence points to the involvement of the cell adhesion molecules, gpIIb-IIIa, P-selectin, CD31, LFA-1, and CD36 in the interaction between platelets and endothelial cells as well as other cell types. The possible role of these molecules in the ability of platelets to support endothelium and to protect against tumour necrosis factor mediated cytolysis or parasitic invasion are reviewed. The involvement of platelets as effectors of tissue damage in cerebral malaria, lipopolysaccharide induced pathology, and pulmonary fibrosis is also discussed. This has then been extended to include the intercellular mechanisms underpinning their pathogenic role in metastasis, transplant rejection, stroke, brain hypoxia, and related conditions. A better understanding of the complex regulation and hierarchical organisation of these various platelet adhesion molecules may prove useful in the development of new approaches to the treatment of such diseases.

Aflatoxin B1 (AFB1) induced rat liver cancer is a well studied system of hepatocarcinogenesis. AFB1 has also been used to transform cultured rat liver derived cells in vitro. Cells in culture often have a reduced capacity to metabolise the AFB1 to its active metabolite, and often prolonged periods of exposure to the toxin have to be employed, with a long latency in the appearance of transformed cells in culture. We report here the transformation of a rat liver derived cell line by acute treatment with AFB1. An extrinsic metabolising system of quail microsomes, which convert AFB1 to its epoxide form with high efficiency, was used to activate the AFB1. A dose dependent cytotoxicity was obtained and neoplastic transformation was seen in the higher doses used. The enzyme GGT which has strong association with liver cell transformation both in vivo and in vitro was also elevated in the treated cells. Images Figure 1